Our objective is to determine the molecular and genetic basis for the differences in Vkappa repertoires expressed by different inbred strains of mice, and to elucidate the detailed structural organization of the mouse Vkappa gene family. The proposed studies bear upon: (1)\the origin of the amino acid sequence diversity of immunoglobulin L chain V regions; (2)\the role, if any, of regulatory phenomena in determining which Vkappa genes will be expressed in an individual and hence, which genes will contribute to antibody responses; (3)\the possibility that the presence in or absence from the germ line of structural genes encoding Vkappa regions, or regulatory phenomena affecting their expression might explain immune response gene (Ir-gene) differences or differences in idiotype expression that map to immunoglobulin loci. Specific aims include: (1)\DNA cloning and characterization at the DNA level of a new group of Vkappa regions, called VkappaSer, and other unique Vkappa groups which are expressed only by mice bearing the Lyt-2a, Lyt-3a genotype. (2)\If genes for Vkappa groups which show strain-specific expressoin are present in the genome of strains which do not express them, we willdetermine by nucleotide sequence analysis whether defects in associated sequences involved in V-J joining, RNA splicing or other functions involved in gene expression may be responsible for their non-expression. (3)\We will determine the arrangement in the germ line of the 4 to 8 Vkappa genes thought to determine a single Vkappa group. We will determine the long range organizationof the Vkappa gene family. These studies should provide information on the evolution, stabilityand possibly the function of the complex Vkappa locus.